The nitric acid esters of organic compounds, common known as nitrated organic compounds, are known and are used as vasodilating agents. Within these, the usefulness of mono and di-nitrated isosorbide is well known, and further there have been described compounds with vascular and coronary activities based on substitution reactions of the free hydroxyl group of isosorbide mononitrate. For example, the U.S. Pat. No. 4,891,373 patent describes derivatives of aminepropanol corresponding to the formulas for the treatment of the angina pectoris and systemic and pulmonary hypertension.
The U.S. Pat. No. 5,665,766 patent describes the isosorbide 5-mononitrate 2-acetylsalicylate, of formula as well as its platelets anti-aggregating activity.
One of the principle problems of the nitrated organic compounds mentioned above resides on the fact that these are quite sensible in relation to the phenomena known as tachyphylaxy or tolerance, which relates to that its effect on the organism decreases during prolonged treatment, and it is then required to sensitively elevate the administered doses in a graduated manner or otherwise to perform a pharmacologically wash out.
It is also known that one way of reducing the tolerance of the nitrated organic compounds consists of introducing a thiol group in the molecule, for example by use of sulphur containing amino acids. The European patent EP-B-0362575 describes nitrated organic compounds with incorporated cysteine and, mainly, methionine molecules.
The patent application WO-A-92/04337 describes organic nitrated derivatives of the ring of the thiazolidine with vasodilating activity and a reduced tolerance.
The patent application WO-A-93/03037 describes an enormously amount of different nitrated organic vasodilating compounds, with reduced tolerance, of highly variable structures, within which are included generically, i.e. without specifying nor describing one single specific product, derivatives of isosorbide mononitrate according to following structure in which R5 represents a hydrogen atom, a C1-C6 alkyl group, a phenyl, etc.
The nitrated organic compounds described in the documents mentioned above do not in itself solve the problems originating from the tolerance of the nitrated organic compounds, since these still have problems in relation to low vasodilating activity, high tolerance, etc. Accordingly, it is still necessary to develop novel nitrated organic compounds which have a high vasodilating activity combined with a more decreased level of tolerance being maintained persistently.